Churg-Strauss Syndrome: Symptoms, Types, Causes and Treatment

Churg-Strauss Syndrome (CSS), also known as eosinophilic granulomatosis with polyangiitis (EGPA), is a rare, complex condition that bridges the worlds of allergy, autoimmunity, and systemic vasculitis. First described in the 1950s, its combination of asthma, high levels of eosinophils, and inflammation of blood vessels can puzzle both patients and doctors alike. Understanding the symptoms, types, causes, and available treatments for CSS is crucial for those affected and for clinicians guiding their care. This article will provide a thorough, evidence-based overview, making the science behind CSS both accessible and actionable.

Symptoms of Churg-Strauss Syndrome

Churg-Strauss Syndrome can manifest with a wide variety of symptoms, often evolving over time. The disease typically progresses through three clinical phases, and its symptoms reflect the organs involved—most commonly the lungs, skin, nervous system, heart, and gastrointestinal tract. Recognizing the key features of CSS is vital for early diagnosis and management.

Symptom	Frequency/Prevalence	Notes/Description	Source(s)
Asthma	Nearly all patients	Usually severe, adult-onset	1 2 6 9 15
Eosinophilia	>90%	Blood eosinophils >10% or >1,500/mm³	1 2 6 9 15
Sinusitis	70%	Maxillary sinusitis, nasal polyps	2 6 9
Skin lesions	40–70%	Purpura, nodules, urticaria	1 2 6 15
Neuropathy	60–75%	Mononeuritis multiplex, polyneuropathy	1 3 4 6 15
Lung Infiltrates	38–77%	Non-fixed, migratory pulmonary infiltrates	1 2 6 9
GI symptoms	37–62%	Abdominal pain, bleeding, diarrhea	1 2 15
Cardiac involvement	13–23%	Myocarditis, pericarditis, heart failure	2 5 9 14 15
Fever, malaise	Frequent	Non-specific systemic symptoms	1 2 15

Table 1: Key Symptoms

Hallmark Symptoms and Disease Phases

Asthma and Eosinophilia:
The most consistent and earliest symptoms are adult-onset asthma and an elevated count of eosinophils in the blood. Asthma is often severe and persistent, sometimes predating other symptoms by years 1 2 6 9 15. Eosinophilia—defined as more than 10% of white blood cells or >1,500 cells/mm³—is a diagnostic cornerstone 1 2 6.

Sinus and Allergic Features:
Many patients also experience chronic sinusitis, nasal polyps, or allergic rhinitis, which often appear alongside or shortly after the onset of asthma 2 6 9.

Systemic and Organ-Specific Manifestations

Vasculitic Phase:
As the disease progresses, systemic inflammation of small- to medium-sized blood vessels leads to more severe symptoms:

• Skin: Rashes, purpura, nodules, and urticaria are frequent 1 2 6 15.
• Nervous System: Peripheral neuropathy, especially mononeuritis multiplex (asymmetric nerve involvement), is found in the majority of patients and can cause pain, numbness, or weakness in the limbs 1 3 4 6 15.
• Lungs: Transient, non-fixed pulmonary infiltrates are common and can be seen on imaging 1 2 6 9.
• Gastrointestinal Tract: Abdominal pain, diarrhea, and bleeding may result from vasculitis of the gut, sometimes leading to severe complications 1 2 15.
• Heart: Cardiac involvement (myocarditis, pericarditis, heart failure) is a major cause of mortality in CSS and may be under-recognized 2 5 9 14 15.
• Renal: Although less common, up to 25% of patients may experience kidney involvement, particularly in those who are ANCA-positive 11.

General Symptoms:
Fever, malaise, weight loss, and muscle or joint aches frequently accompany the above features 1 2 15.

Types of Churg-Strauss Syndrome

While CSS is a single disease entity, recent research highlights that its clinical presentation can vary widely, often depending on underlying immunological markers. Understanding these "subtypes" helps tailor therapy and predict complications.

Type/Pattern	Distinguishing Features	Associated Markers/Factors	Source(s)
ANCA-Positive	Renal, peripheral nerve, CNS involvement	MPO-ANCA, higher vasculitic risk	2 5 7 9 11 13
ANCA-Negative	Cardiac involvement predominates	Eosinophilic tissue infiltration	5 9
Classic CSS	Asthma, eosinophilia, vasculitis	All or most diagnostic criteria	6 9 15
Severe Organ Involvement	Cardiac, GI, CNS complications	Poor prognosis (FFS ≥1)	9 14 15

Table 2: Clinical Types/Patterns

ANCA-Positive vs. ANCA-Negative CSS

ANCA-Positive Subtype:
Roughly one-third to half of CSS patients test positive for antineutrophil cytoplasmic antibodies (ANCAs), especially those targeting myeloperoxidase (MPO-ANCA). These patients are more likely to have:

• Kidney involvement (such as necrotizing crescentic glomerulonephritis)
• Peripheral neuropathy
• Central nervous system involvement
  2 5 7 9 11 13

ANCA-Negative Subtype:
Those lacking ANCAs tend to have more prominent heart disease (cardiomyopathy) and are more likely to experience complications from tissue eosinophilia rather than vasculitis per se 5 9. This distinction may influence both prognosis and treatment choices.

Severity-Based Stratification

Classic/Typical CSS:
Most patients present with a combination of asthma, eosinophilia, and manifestations of small-vessel vasculitis. Meeting four or more of the six American College of Rheumatology criteria strongly supports the diagnosis 6 9 15.

Severe Forms:
Patients with significant cardiac, gastrointestinal, or central nervous system involvement are considered at high risk for poor outcomes. The French Vasculitis Study Group’s "Five-Factor Score" is often used to stratify risk and guide therapy 9 14 15.

Causes of Churg-Strauss Syndrome

The exact cause of CSS remains elusive, but advances in immunology, genetics, and epidemiology have shed light on its complex pathogenesis. Both environmental and intrinsic factors play a role, with the immune system at the center of disease development.

Cause/Factor	Description/Role	Evidence/Notes	Source(s)
Immune Dysregulation	Th2-mediated, eosinophilic response	Asthma, allergy, eosinophilia	2 5 9 8
ANCA Autoimmunity	Autoantibodies against MPO	Vasculitic organ damage	2 5 7 9 11 13
Environmental Triggers	Drugs, vaccines, allergens	Suspected, not proven	2 7 8 10
Genetic Predisposition	Likely, not well-defined	Under investigation	5 9

Table 3: Major Causes and Contributing Factors

Immunological Mechanisms

Allergy and Th2 Dominance:
CSS is classically a Th2-dominated disease, meaning the immune system is skewed toward allergic-type responses. This results in:

• High levels of eosinophils in blood and tissues
• Increased cytokines like interleukin-5 (IL-5), which promote eosinophil survival
  2 5 9

ANCA-Associated Vasculitis:
In a subset of patients, the immune system forms autoantibodies (ANCAs) targeting myeloperoxidase (MPO) in white blood cells. These antibodies contribute to inflammation and destruction of vessel walls, leading to classic vasculitis features such as glomerulonephritis and neuropathy 2 5 7 9 11 13.

Environmental and Drug Triggers

Some cases of CSS appear to be triggered by exposures such as:

• Certain medications (notably leukotriene receptor antagonists used in asthma treatment)
• Vaccinations or allergen desensitization therapies

While these associations have been reported, causality has not been definitively established. Most evidence suggests these may act as triggers in susceptible individuals rather than primary causes 2 7 8 10.

Genetic and Other Factors

A genetic predisposition is likely, though no specific genes have been conclusively identified. Ongoing research is investigating both genetic and environmental contributors to CSS risk 5 9.

Treatment of Churg-Strauss Syndrome

Treating CSS is a balancing act: suppressing inflammation to prevent organ damage, while minimizing medication side effects. The mainstay of therapy is corticosteroids, but immunosuppressive agents and novel biologic drugs have important roles, especially in severe or refractory cases.

Treatment	Indication/Use	Notes/Effectiveness	Source(s)
Corticosteroids	All patients, initial therapy	Most achieve remission; relapses common	1 2 8 9 15
Cyclophosphamide	Severe organ involvement	Used with steroids in high-risk cases	1 2 9 14 15
Immunosuppressants	(Azathioprine, MTX, etc.)	Maintenance, steroid-sparing	2 9 15
Biologics	Refractory or relapsing disease	Mepolizumab (anti-IL-5), Rituximab	5 9 12 13
IVIG	Resistant cardiac/neural disease	Used when standard therapy fails	14

Table 4: Main Treatment Strategies

Standard Therapy

Corticosteroids:
High-dose oral or intravenous steroids are the first-line treatment. Most patients enter remission, but up to 25% experience relapses, and many require long-term, low-dose steroids to control asthma 1 2 8 9 15.

Immunosuppressive Agents:
For patients with severe organ involvement (heart, GI tract, nervous system, or kidneys), cyclophosphamide is added to steroids. Other immunosuppressants (azathioprine, methotrexate) may be used for maintenance or as steroid-sparing agents 1 2 9 14 15.

Targeted and Advanced Therapies

Biologic Agents:
Biologics are emerging as promising options, particularly for patients who are refractory to standard treatment or who wish to reduce steroid exposure.

• Mepolizumab: An anti-IL-5 antibody, it targets eosinophilic inflammation and has been shown to reduce steroid requirements and disease activity 5 9 12.
• Rituximab: An anti-CD20 antibody that depletes B cells, used especially in ANCA-positive patients with kidney involvement 5 9 13.

IVIG (Intravenous Immunoglobulin):
IVIG may benefit patients with severe heart or nerve involvement who do not respond to steroids and cyclophosphamide. It can improve cardiac function and neuropathy in resistant cases 14.

Monitoring and Prognosis

• Most patients respond well to therapy and have a good long-term prognosis, with 5- to 10-year survival rates exceeding 75–90% 1 2 5 9 15.
• Relapses are common, especially during attempts to taper steroids.
• Patients with severe cardiac or GI involvement have the highest risk of complications and mortality 1 2 5 9 14 15.

Individualized Approaches

Treatment is tailored based on severity, organ involvement, ANCA status, and patient preferences. Close monitoring and adjustment of therapy are essential to prevent relapses and minimize long-term side effects.

Conclusion

Churg-Strauss Syndrome is a rare but treatable disorder that straddles the intersection of allergy, autoimmunity, and systemic vasculitis. Prompt recognition and individualized therapy can dramatically improve outcomes.

Key points:

• CSS typically presents with adult-onset asthma, marked eosinophilia, and systemic vasculitis affecting multiple organs.
• Clinical manifestations are diverse; the lungs, skin, nerves, heart, and GI tract are most commonly involved.
• Disease subtypes (ANCA-positive vs. negative) influence organ involvement and prognosis.
• The cause is multifactorial, involving immune dysregulation, autoantibodies, and possible environmental triggers.
• Corticosteroids are the cornerstone of therapy, with immunosuppressants and biologics reserved for severe or refractory cases.
• Long-term outlook is generally favorable, but vigilant monitoring is needed to manage relapses and complications.

Awareness and understanding of Churg-Strauss Syndrome among patients and clinicians are crucial for timely diagnosis and effective management, ensuring the best possible quality of life for those affected.